T cells bearing invariant gamma delta T cell antigen receptors (TCR) localize to distinct epithelial sites in the adult mouse. The Thy-1+ dendritic epidermal T cells (DETC) express a monoclonal Vgamma3Vdelta1 TCR that is not found elsewhere. We have demonstrated that the DETC recognize and respond to self antigens expressed by neighboring keratinocytes after damage or disease. This antigen recognition is mediated by the DETC gammadelta TCR. DETC play a unique role in tissue repair following recognition of wounded keratinocytes. Interestingly, DETC do not express coreceptors CD4 or CD8 and do not express the costimulatory receptor CD28. We hypothesize that molecules in addition to the TCR are involved in DETC antigen-mediated responses. We have identified Plexin-B2 as a molecule expressed by keratinocytes that affects DETC function, potentially, through binding CD 100 expressed by DETC. Ligation of CD 100 on DETC may facilitate recognition of damaged keratinocytes leading to DETC activation and participation in local immune responses including tissue homeostasis and repair. We will test the hypothesis that Plexin-B2 expressed by keratinocytes binds to CD 100 on DETC to deliver signals that are required for DETC function. We will determine if Plexin-B2 on keratinocytes and CD 100 on DETC deliver costimulatory signals to DETC. We will determine if there is a receptor-ligand pairing of Plexin-B2 with CD 100. We will determine the roles of Plexin-B2 and CD 100 in DETC function. Together these studies should determine the roles of these molecules in DETC activation and function and may be applicable for other gamma delta T cell populations.